| IED ID | IndEnz0010000785 |
| Enzyme Type ID | esterase000785 |
| Protein Name |
Poly ADP-ribose glycohydrolase EC 3.2.1.143 |
| Gene Name | Parg |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MSAGPGWEPCTKRPRWGAAGTSAPTASDSRSFPGRQRRVLDPKDAPVQFRVPPSSPACVSGRAGPHRGNATSFVFKQKTITTWMDTKGPKTAESESKENNNTRIDSMMSSVQKDNFYPHKVEKLENVPQLNLDKSPTEKSSQYLNQQQTASVCKWQNEGKHAEQLLASEPPAGTPLPKQLSNANIGQSPHTDDHSDTDHEEDRDNQQFLTPIKLANTKPTVGDGQARSNCKCSGSRQSVKDCTGCQQEEVDVLPESPLSDVGAEDIGTGPKNDNKLTGQESSLGDSPPFEKESEPESPMDVDNSKNSCQDSEADEETSPVFDEQDDRSSQTANKLSSCQAREADGDLRKRYLTKGSEVRLHFQFEGENNAGTSDLNAKPSGNSSSLNVECRSSKQHGKRDSKITDHFMRISKSEDRRKEQCEVRHQRTERKIPKYIPPNLPPEKKWLGTPIEEMRKMPRCGIHLPSLRPSASHTVTVRVDLLRAGEVPKPFPTHYKDLWDNKHVKMPCSEQNLYPVEDENGERTAGSRWELIQTALLNKFTRPQNLKDAILKYNVAYSKKWDFTALVDFWDKVLEEAEAQHLYQSILPDMVKIALCLPNICTQPIPLLKQKMNHSVTMSQEQIASLLANAFFCTFPRRNAKMKSEYSSYPDINFNRLFEGRSSRKPEKLKTLFCYFRRVTEKKPTGLVTFTRQSLEDFPEWERCEKPLTRLHVTYEGTIEGNGRGMLQVDFANRFVGGGVTGAGLVQEEIRFLINPELIVSRLFTEVLDHNECLIITGTEQYSEYTGYAETYRWARSHEDGSEKDDWQRRCTEIVAIDALHFRRYLDQFVPEKVRRELNKAYCGFLRPGVPSENLSAVATGNWGCGAFGGDARLKALIQILAAAAAERDVVYFTFGDSELMRDIYSMHTFLTERKLDVGKVYKLLLRYYNEECRNCSTPGPDIKLYPFIYHAVESSAETTDMPGQKAGT |
| Enzyme Length | 969 |
| Uniprot Accession Number | O88622 |
| Absorption | |
| Active Site | ACT_SITE 730; /evidence=ECO:0000250|UniProtKB:Q86W56; ACT_SITE 748; /evidence=ECO:0000250|UniProtKB:Q86W56; ACT_SITE 749; /evidence=ECO:0000250|UniProtKB:Q86W56 |
| Activity Regulation | |
| Binding Site | BINDING 733; /note=Substrate; /evidence=ECO:0000250|UniProtKB:Q86W56; BINDING 747; /note=Substrate; via amide nitrogen; /evidence=ECO:0000250|UniProtKB:Q86W56; BINDING 788; /note=Substrate; /evidence=ECO:0000250|UniProtKB:Q9QYM2 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=[(1''->2')-ADP-alpha-D-ribose](n) + H2O = [(1''->2')-ADP-alpha-D-ribose](n-1) + ADP-D-ribose; Xref=Rhea:RHEA:52216, Rhea:RHEA-COMP:16922, Rhea:RHEA-COMP:16923, ChEBI:CHEBI:15377, ChEBI:CHEBI:57967, ChEBI:CHEBI:142512; EC=3.2.1.143; Evidence={ECO:0000250|UniProtKB:Q86W56}; |
| DNA Binding | |
| EC Number | 3.2.1.143 |
| Enzyme Function | FUNCTION: Poly(ADP-ribose) glycohydrolase that degrades poly(ADP-ribose) by hydrolyzing the ribose-ribose bonds present in poly(ADP-ribose). PARG acts both as an endo- and exoglycosidase, releasing poly(ADP-ribose) of different length as well as ADP-ribose monomers. It is however unable to cleave the ester bond between the terminal ADP-ribose and ADP-ribosylated residues, leaving proteins that are mono-ADP-ribosylated. Poly(ADP-ribose) is synthesized after DNA damage is only present transiently and is rapidly degraded by PARG. Required to prevent detrimental accumulation of poly(ADP-ribose) upon prolonged replicative stress, while it is not required for recovery from transient replicative stress. Responsible for the prevalence of mono-ADP-ribosylated proteins in cells, thanks to its ability to degrade poly(ADP-ribose) without cleaving the terminal protein-ribose bond. Required for retinoid acid-dependent gene transactivation, probably by removing poly(ADP-ribose) from histone demethylase KDM4D, allowing chromatin derepression at RAR-dependent gene promoters. Involved in the synthesis of ATP in the nucleus, together with PARP1, NMNAT1 and NUDT5. Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming. {ECO:0000250|UniProtKB:Q86W56}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Alternative sequence (2); Beta strand (19); Binding site (3); Chain (1); Compositional bias (8); Erroneous termination (2); Helix (24); Modified residue (12); Motif (2); Region (7); Sequence conflict (5); Turn (8) |
| Keywords | 3D-structure;Acetylation;Alternative splicing;DNA damage;Hydrolase;Nucleus;Phosphoprotein;Reference proteome |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q86W56}. Note=Colocalizes with PCNA at replication foci. Relocalizes to the cytoplasm in response to DNA damage (By similarity). {ECO:0000250|UniProtKB:Q86W56}. |
| Modified Residue | MOD_RES 135; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:21183079"; MOD_RES 137; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:21183079"; MOD_RES 195; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q86W56"; MOD_RES 197; /note="Phosphothreonine"; /evidence="ECO:0000250|UniProtKB:Q86W56"; MOD_RES 256; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:17242355, ECO:0007744|PubMed:21183079"; MOD_RES 259; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:17242355, ECO:0007744|PubMed:21183079"; MOD_RES 281; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q86W56"; MOD_RES 286; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"; MOD_RES 293; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:21183079"; MOD_RES 297; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:21183079"; MOD_RES 311; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q86W56"; MOD_RES 334; /note="N6-acetyllysine"; /evidence="ECO:0007744|PubMed:23806337" |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (7) |
| Cross Reference PDB | 4FC2; 4N9Y; 4N9Z; 4NA0; 4NA4; 4NA5; 4NA6; |
| Mapped Pubmed ID | 11171322; 12466851; 12520002; 14685157; 15282315; 15591342; 15677308; 15725727; 15791006; 16526943; 17116882; 17157196; 17276427; 17640816; 18799693; 19262751; 19264700; 19319190; 20878536; 20881315; 20926829; 21228215; 21267068; 21366272; 21398629; 23102699; 23624507; 24191052; 24194600; 24465839; 24664732; 24810616; 24853412; 26496610; 29589839; 30864743; 31130856; |
| Motif | MOTIF 10..16; /note=Nuclear localization signal; /evidence=ECO:0000250|UniProtKB:Q86W56; MOTIF 77..84; /note=PIP-box (PCNA interacting peptide); /evidence=ECO:0000250|UniProtKB:Q86W56 |
| Gene Encoded By | |
| Mass | 109,324 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:52216 |
| Cross Reference Brenda | 3.2.1.143; |